(MRC DTP) Great expectations: Understanding the role of neuronal activity in early postnatal development in determining stroke outcome

Brain building is a protracted process that lasts for several weeks in rodents but years in humans. Although this process is continuous, there are critical time windows during brain development that are particularly vulnerable to insults. Alterations occurring during these critical time windows can have a long-lasting impact throughout the lifespan of the organism. These alterations although differing in origins (e.g. genetic mutations, environmental insults), may converge onto a similar molecular mechanism such as alteration in neuronal activity during early development. Such changes in neuronal activity have been reported in individuals diagnosed with neurodevelopmental disorders such as autism spectrum disorders (ASD)1. This suggests that aberrant changes in neuronal activity during early development can alter how brains are formed and function in later life. It has been recently reported that in a twin study, twins that have been diagnosed with ASD are more likely to have increased neurological conditions (e.g. headaches, epilepsy) compared to twins that were not diagnosed with ASD2. This suggests that deviation in how brains are formed during development may increase the susceptibility of individuals to other neurological conditions. What is unknown however, is the extent of how such changes during early development can impact individual susceptibility or responses to other neurological conditions when challenged in later life such as in stroke. While these early aberrations in neuronal activity may not induce the stroke itself, it may however alter the susceptibility of the individual or the severity of the stroke. If this hypothesis holds true, early detection of aberrant neuronal activity during development may provide an opportunity for preventive treatment or delay the onset of certain neurological conditions. Consequently, the main objective of this project is to examine the link between neurodevelopment and neurological conditions in later life by studying the impact of aberrant neuronal activity in early postnatal development on the neurological outcome in a stroke model.

The project will use a wide range of techniques such as chemogenetics, stroke models, in vivo imaging, and electrophysiology in order to elucidate how susceptibility to neurological conditions may be attributed to alterations in brain formation during critical periods in development. This project will take advantage of the expertise of several labs by combining the Wong’s lab experience in embryonic and postnatal development, the Allan lab’s in neuroninflammation and stroke models, the Petersen’s lab in sensory coding and the Schiessl’s lab on in vivo imaging of neurovascular function.

Fong Kuan Wong
https://www.fongkuanwonglab.com

Stuart Allan
https://www.research.manchester.ac.uk/portal/stuart.allan.html

Rasmus Petersen
https://www.research.manchester.ac.uk/portal/r.petersen.html

Ingo Shiessl
https://www.research.manchester.ac.uk/portal/i.schiessl.html


Entry Requirements:
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

UK applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).

If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.

Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the MRC Doctoral Training Partnership (DTP) website www.manchester.ac.uk/mrcdtpstudentships